Methyl 6-methylsalicylate

Mayriella overbecki W-PG Trail following Methyl 6-methylsalicylate 68 [180]... 

Within Hymenoptera, pheromones produced by workers in social colonies are the best studied across many genera, principally in ants [6], with those eliciting trail following most extensively studied. The distinct behavior and the relative ease of the bioassay have resulted in chemical identifications in many species [ 113,114]. Those that have been recently identified are listed in Table 5. In addition, several alarm and recruitment signals have recently been identified. Many of the compounds recently identified in ants have previously been reported as trail or alarm pheromones in other ant species. For example, methyl 4-methylpyrrole-2-carboxylate 64, 3-ethyl-2,5-dimethylpyrazine 65, (9Z)-hexadec-9-enal 66,4-methylheptan-3-ol 67, and methyl 6-methylsalicy-late 68 have been identified as trail pheromone components, and heptan-2-one 69,4-methylheptan-3-one 70, formic acid 71, undecane 61,4-methylheptan-3-ol 67, methyl 6-methylsalicylate 68, and citronellal 72 have been identified as alarm pheromone components [6]. The use of the same chemicals across genera, with some used for very different functions, is an interesting phenomenon. 

From recent work, we do know that chemical signals from the seeds direct the ants selections. Although the story is still incomplete, an extraordinary finding has been that a chemical compound called MMS (methyl 6-methylsalicylate) is present in the seeds the ants choose. MMS is found in the seeds of the ten or twelve unconnected species from seven plant families that flourish in Peruvian ant gardens. The ants seem to find this compound irresistible. Offered inert particles coated with MMS, they become excited, pick up these decoy seeds, and occasionally carry them about. 

The sex pheromone of the slave-making ant, Polyergus breviceps, has been identified as a blend of methyl-6-methylsalicylate and 3-ethyl-4-methylpentanol. Each compound alone was completely unattractive to males whereas a blend of the two compounds attracted hundreds of males in a couple of hours. 

Methyl 6-methylsalicylate is the trail pheromone of some ants, it is also found in carabid beetle, 6-methylsalicylaldehyde in the defensive secretion of a cerambycid beetle, and 6-methylsalicylic acid is made by some Penicillium moulds. Orsellinic acid and 6-methylsalicylic acid are... 

Figure 5.8 Part of the mass spectrum of the pheromone methyl 6-methylsalicylate, and the spectrum after incubation with deuterated S-adenosylmethionine, showing molecular ions at 166 atul 169 in a ratio of 85 15...

The tri-deuterated S-adenosylmethionine is almost 100% pure. Essentially all the hydrogens in the methyl group have been replaced by deuterium. How much of the deuterated methyl group finds its way into methyl 6-methylsalicylate may be very small. Isotopic enrichment refers to the change in isotope content in the biosynthesized compound above the natural abundance and is usually expressed as atom % excess. The isotopic enrichment of the methyl group in the pheromone can be estimated from the relative abundances of the peaks at m/z 166 and 169 (Figure 5.8). The ratio is 1 0.18. The enrichment is then 15%. 

Figure 5.9 The use of C NMR spectroscopy in demonstrating the labelling of the methyl ester of methyl 6-methylsalicylate. (a) The proton-decoupled spectrum of the unlabelled compound, (b) Substitution of deuterium for hydrogen on a methyl group causes C-H coupling and a small upfield shift (0.9 Hz) for CD3.

Phoracantha species contained 6-methylsalicylic aldehyde 191, the dis-ubstituted cyclopentene phoracanthal 192, the corresponding alcohol, phora-canthol, and the (E)- and (Z)-stereoisomers of the saturated system. In addition, methyl and ethyl esters of 2-methylbutyric acid and isovaleric acid as well as the macrocyclic lactones decan-9-olide (=phoracantholide I), (Z)-dec-4-en-9-olide (=phoracantholide J) 193, and 11 -hydroxytetradec-5-en-13-olide 194 [8,355, 356]. As shown by independent syntheses of both enantiomers, the natural phoracantholides show ( -configuration [357]. 

The minor constituents like methyl amyl ketone, methylsalicylate, etc., are responsible for the characteristic pleasant odour of cloves. The oil is dominated by eugenol (70-85%), eugenyl acetate (15%) and /Tcaryophyllene (5-12%), which together make up 99% of the oil. /3-Caryophyllene, which was earlier thought of as an artefact of distillation, was first reported as a constituent of the bud oil by Walter (1972). 

Dimroth P, Greull G, Seyfferet R, Lynen F (1972) Hoppe Syler s Z Physiol Chem 353 126 Dimroth P,Ringelmann E, Lynen F (1976) Eur J Biochem 68 591 Bhogal P, Shoolingin-Jordan P. Incorporation of novel substrates into 6-methylsalicylic acid and triacetic acid lactone analogues by 6-methyl salicylic acid synthase. In Polyketides chemistry, biochemistry, molecular genetics. 1996. Royal Society of Chemistry, Bristol, UK, p 19... 

For the preparation of methyl vinylsalicylates (3-, It-, 5-isomers) both synthetic routes were used. Methyl 5-vinylsalicylate was synthesized in about 50 overall yield from methylsalicylate by the first route (dehydration) (15), the synthesis of methyl 3-vinylsali-cylate (16) and methyl It—vinylsalicylate (l ) starting from 2-ethyl-... 

Phenols substituted by the 2-hydroxymethyl group represent the monomers of phenol/formaldehyde polymers and their regio specific synthesis has received extensive experimental study. A number of preparations are Used in Table 6.3 (refs.27-33). The alkyl methyl ether of o-methylsalicyl alcohol [2-(1 -methoxyethyl)phenol] has been formed in a yield of 12% from a mixture of phenol and 1,1-dimethoxyethane (1 10) by passage at 250 C with helium as carrier gas through a fixed bed catalyst of an H-ZSM-5 zeolite proton exchangeable) supported on glass wool with a contact time of 6.9 secs. (ref.34). 

Methyl 5-methylsalicylate has been obtained in 71% yield by intramolecular cyclisation of the open-chain ketoester, methyl 6-methylene-3-oxoheptanoate in acetic acid containing 4 equivs. manganese(lli) acetate dihydrate and 4 equivs. iithium chloride at ambient temperature during 24 hours followed by heating of the crude product with lithium chloride at 100°C for 24 hours (ref.38). 

Successful approaches to the stereoselective total synthesis of AI-77-B (28) have been reported recently by several groups. The first total synthesis was reported by Hamada et al (ref.125,126). The aminodihydroisocoumarin (42) was prepared from ethyl 6-methyIsalicylate and W-protected (S)-leucinal by a process involving diastereoselective 1,2-addition of the benzylic anion followed by spontaneous lactone formation (Scheme 4). Briefly, the methoxymethyl (MOM) methyl ester (61) was prepared from ethyl 6-methylsalicylate in the usual manner. The benzylic anion (62) was then generated in situ, by reaction of (61) with lithium diisopropy1 amide (LDA) in the presence of tetramethylethylenediamine (TMEDA) in THF (-78°C/lhr), and reacted with Boc-(S)-leucinal (63). This afforded a separable mixture of diastereomers (64a and 64b) in 32% yield. Upon use of excess LDA (2.6 equiv.) and (63) (1.4 equiv.) an 81 19 stereoselectivity was... 

Synonyms o-Anisic acid, methyl ester Benzoic acid, 2-methoxy-, methyl ester Dimethyl salicylate o-Methoxybenzoic acid methyl ester o-M ethoxy methyl benzoate Methyl o-anisate Methyl 2-methoxybenzoate Methylsalicylate methyl ester Empiricai C9H10O3 Formuia CH3OC6H4CO2CH3 Properties M.w. 166.18 dens. 1.157 b.p. 248 C flash pt. > 230 F ref. index 1.5340 Toxicology LD50 (oral, rat) 3800 mg/kg, (skin, rabbit) > 5 g/kg mod. toxic by ing. si. toxic by skin contact TSCA listed Hazardous Decomp. Prods. Heated to decomp., emits acrid smoke and irritating vapors Uses Synthetic flavoring agent in foods and pharmaceuticals... 

Since fatty acid and aromatic synthetases have many properties in common, it is interesting to consider the effect of omitting NADPH from incubations catalyzed by these enzymes and to examine the consequences. In all cases studied from animal (Bressler and Wakil, 1%2 Nixon et al., 1%8), yeast (Yalpani et al., 1969), and bacterial origin (Brock and Bloch, 1966), fatty acid synthesis is naturally abolished, but a Q compound, triacetic acid lactone (4-hydroxy-6-methyl-2-pyrone) (VII), is formed instead. This product is also made when the NADPH-requiring 6-methylsalicylate synthetase is deprived of this nucleotide (Dimroth et al., 1972), but the relative rate of synthesis is considerably greater than that produced by fatty acid synthetase in P. patulum (Yalpani et al., 1%9). However, Scott et al. (1971) have reported that triacetic acid lactone is also formed by 6-methylsalicylate synthetase, albeit at a reduced rate, even in the presence of NADPH. 

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